An introduction to immunology and immunopathology

Hypersensitivity reactions

Hypersensitivity reactions refer to undesirable responses 

produced by the normal immune system. There are four 

types of hypersensitivity reactions [

6

, 

7

]:

  • Type I: immediate hypersensitivity.

  • Type II: cytotoxic or antibody-dependent hypersensitivity.

  • Type III: immune complex disease.

  • Type IV: delayed-type hypersensitivity.

Type I hypersensitivity is the most common type 

of hypersensitivity reaction. It is an allergic reaction 

provoked by re-exposure to a specific type of antigen, 

referred to as an allergen. Unlike the normal immune 

response, the type I hypersensitivity response is 

characterized by the secretion of IgE by plasma cells. 

IgE antibodies bind to receptors on the surface of 

tissue mast cells and blood basophils, causing them 

to be “sensitized”. Later exposure to the same allergen 

cross-links the bound IgE on sensitized cells resulting 

in degranulation and the secretion of active mediators 

such as histamine, leukotrienes, and prostaglandins that 

cause vasodilation and smooth-muscle contraction of the 

surrounding tissue. Common environmental allergens 

inducing IgE-mediated allergies include pet (e.g., cat, 

dog, horse) epithelium, pollen, house dust mites, and 

molds. Food allergens are also a common cause of type 

I hypersensitivity reactions, however, these types of 

reactions are more frequently seen in children than 

adults. Treatment of type I reactions generally involves 

trigger avoidance, and in the case of inhaled allergens, 

pharmacological intervention with bronchodilators, 

antihistamines and anti-inflammatory agents. Some types 

of allergic disease can be treated with immunotherapy 

(see  Allergen-specific Immunotherapy article in this 

supplement). Severe cases of type 1 hypersensitivity 

(anaphylaxis) may require immediate treatment with 

epinephrine.

Type II hypersensitivity reactions are rare and take 

anywhere from 2 to 24  h to develop. These types of 

reactions occur when IgG and IgM antibodies bind 

to the patient’s own cell-surface molecules, forming 

complexes that activate the complement system. This, in 

turn, leads to opsonization, red blood cell agglutination 

(process of agglutinating or “clumping together”), cell 

lysis and death. Some examples of type II hypersensitivity 

reactions include: erythroblastosis fetalis, Goodpasture 

syndrome, and autoimmune anemias.

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Type III hypersensitivity reactions occur when IgG and 

IgM antibodies bind to soluble proteins (rather than cell 

surface molecules as in type II hypersensitivity reactions) 

forming immune complexes that can deposit in tissues, 

leading to complement activation, inflammation, 

neutrophil influx and mast cell degranulation. This type 

of reaction can take days, or even weeks, to develop and 

treatment generally involves anti-inflammatory agents 

and corticosteroids. Examples of type III hypersensitivity 

reactions include systemic lupus erythematosus (SLE), 

serum sickness and reactive arthritis.

Unlike the other types of hypersensitivity reactions, 

type IV reactions are cell-mediated and antibody-

independent. They are the second most common type 

of hypersensitivity reaction and usually take 2 or more 

days to develop. These types of reactions are caused 

by the overstimulation of T cells and monocytes/

macrophages which leads to the release of cytokines 

that cause inflammation, cell death and tissue damage. 

In general, these reactions are easily resolvable through 

trigger avoidance and the use of topical corticosteroids. 

An example of this is the skin response to poison ivy.

A brief summary of the four types of hypersensitivity 

reactions is provided in Table 

3

.